MSC-Derived Exosome Promotes M2 Polarization and Enhances Cutaneous Wound Healing
MSC-Derived Exosome Promotes M2 Polarization and Enhances Cutaneous Wound Healing
复制标题
MSC 衍生的外泌体促进 M2 极化并增强皮肤伤口愈合
DOI：
10.1155/2019/7132708
复制
发表时间：
2019-09-09
影响因子：
4.3
通讯作者：
Li, Bei
中科院分区：
文献类型：
--
作者：
He, Xiaoning;Dong, Zhiwei;Li, Bei
间充质干细胞移植（MSCT）促进皮肤伤口愈合。大量研究表明，MSCT的治疗效果似乎是由旁分泌信号介导的。然而，在皮肤伤口愈合区域中，在MSCT期间MSC和巨噬细胞之间的细胞-细胞相互作用仍然是未知的。在这项研究中，早期耗尽的巨噬细胞延迟了MSC注射的伤口修复，这表明MSC介导的伤口愈合需要巨噬细胞。此外，我们证明了全身输注的骨髓间充质干细胞（BMMSCs）和颌骨骨髓间充质干细胞（JMMSCs）可以易位到伤口部位，促进巨噬细胞向M2极化，并促进伤口愈合。在体外与巨噬细胞共培养的骨髓间充质干细胞增强其M2极化。从机制上讲，我们发现来源于MSC的外泌体诱导巨噬细胞极化，并且MSC的外泌体的耗尽降低了巨噬细胞的M2表型。输注不含外来体的MSC导致伤口部位沿着较低数量的M2巨噬细胞以及延迟的伤口修复。我们进一步表明，来源于MSC外泌体的miR-223通过靶向pknox 1调节巨噬细胞极化。这些发现提供了证据表明，MSCT促进了巨噬细胞的M2极化，并可能通过转移外泌体衍生的microRNA加速伤口愈合。
Mesenchymal stem cell transplantation (MSCT) promotes cutaneous wound healing. Numerous studies have shown that the therapeutic effects of MSCT appear to be mediated by paracrine signaling. However, the cell-cell interaction during MSCT between MSCs and macrophages in the region of cutaneous wound healing is still unknown. In this study, early depletion of macrophages delayed the wound repair with MSC injection, which suggested that MSC-mediated wound healing required macrophages. Moreover, we demonstrated that systemically infused bone marrow MSCs (BMMSCs) and jaw bone marrow MSCs (JMMSCs) could translocate to the wound site, promote macrophages toward M2 polarization, and enhance wound healing. In vitro coculture of MSCs with macrophages enhanced their M2 polarization. Mechanistically, we found that exosomes derived from MSCs induced macrophage polarization and depletion of exosomes of MSCs reduced the M2 phenotype of macrophages. Infusing MSCs without exosomes led to lower number of M2 macrophages at the wound site along with delayed wound repair. We further showed that the miR-223, derived from exosomes of MSCs, regulated macrophage polarization by targeting pknox1. These findings provided the evidence that MSCT elicits M2 polarization of macrophages and may accelerate wound healing by transferring exosome-derived microRNA.